A competitive renewal is submitted for the EHS Center in "Molecular and Cellular Toxicology with Human Applications" headquartered in the Institute of Environmental Health Sciences (IEHS) at Wayne State University (WSU). The focus of the Center is the stimulation of collaborative interdisciplinary, multidisciplinary research employing contemporary molecular, cellular, genomic and proteomic approaches to the study of environmental agent (e.g. organochlorines/PAH/solvents and particulates; major urban/Southeastern Michigan concerns) effects on gene expression, cell signaling and function, and human populations. Disease emphasis includes asthma, hepatic dysfunction in metabolic diseases (e.g. diabetes, inflammation, dislipidemias), reproductive and neurological disorders, and cancer. Progress includes 12 multi-investigator grants ($43 M), numerous collaborative grants, 93 collaborative and 411 total publications, research integrating population and bench scientists, and institutional investment. The EHS Center consists of an Administrative Core, three Research Cores, four Facility Cores, a COEP, a Pilot Project Program and an Enrichment Program. The Research Cores, "Gene Regulation and Genetics", "Cell Signaling and Function" and "Environmental Epidemiology", contain 43 faculty from three schools/colleges, three centers and five departments. The "Cell Culture", "Imaging and Cytometry", "Microarray and Bioinformatics" and "Protein Interaction and Proteomics" Facility Cores exist in dedicated space with assigned personnel to support research. The Microarray and Bioinformatics Facility Core includes Agilent and ABI equipment, Sun computers, analysis software (e.g. Rosetta Resolver(R) and bioinformatics expertise to assist with global gene expression analysis and the association of genetic factors (i.e. SNPs (polymorphisms), mutations) with disease. A Protein Interaction and Proteomics Facility Core has been initiated with the purchase of major equipment. An active COEP, with emphasis on K-12 education, has been developed and includes K-12 curricula, science camps, competitive science awards, high school teacher training, and dissemination of information to the community. The Pilot Project Program contains escalating incentive funding for collaborative, interdisciplinary, multidisciplinary research proposals; supplemental funds for scored, not funded, grants may be provided. Professional growth is stimulated through an Enrichment Program (i.e. a seminar series and an Annual Thematic Symposium offering Category I Continuing Medical Education credits). Institutional commitment is shown by the hierarchal position of the IEHS in WSU, by assigned tenure track positions, by approximately $1,000,000 in equipment purchases, and by past (approximately $240,000) and future cost sharing of the Pilot Project Program (approximately $300,000). The EHS Center, reviewed annually by the External Advisory Board, provides Center Members with the opportunity and resources for collaborative interdisciplinary/multidisciplinary research, involving bench scientists, bioinformaticists, structural biologists, population scientists, physician-scientists and graduate students, to examine the role of environmental agents in disease.